Pharmacodynamic Assessment of Cefprozil against Streptococcus pneumoniae: Implications for Breakpoint Determinations
AUTOR(ES)
Nicolau, David P.
FONTE
American Society for Microbiology
RESUMO
Cefprozil, an oral semisynthetic cephalosporin, is commonly utilized in the treatment of respiratory-tract infections in children. While this agent has provided acceptable clinical success over a number of years, this study was undertaken to better define its pharmacodynamic profile against Streptococcus pneumoniae. Nineteen clinical isolates of S. pneumoniae were utilized in the neutropenic murine thigh infection model. To simulate the pharmacokinetic profile of cefprozil in children, the renal function of mice was impaired with uranyl nitrate, and a commercially available cefprozil suspension (6 mg/kg of body weight) was administered orally every 12 h. Mice were infected with 106 to 107 CFU per thigh, and therapy was initiated 2 h later. At 0 and 24 h postinfection, thighs were harvested to determine bacterial density. Survival was assessed during 96 h of therapy. The magnitude of bacterial kill ranged from 0.5 to 4.4 log10 CFU per thigh over 24 h, and the extent of microbial eradication was dependent on the MIC. Killing of more than 2.6 log10 CFU per thigh was observed with MICs of ≤3 μg/ml, while either minimal killing or growth was detected with MICs of ≥4 μg/ml. Mortality in untreated control animals was 100%. Animals infected with strains for which the MICs were ≤2 μg/ml survived the infection, whereas MICs exceeding 2 μg/ml resulted in substantial mortality. These studies demonstrate the effectiveness of cefprozil against isolates of the pneumococcus for which the MICs are ≤2 μg/ml using a drug exposure typically observed in children. These data support a susceptibility breakpoint of ≤2 μg/ml for cefprozil.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=89857Documentos Relacionados
- In Vivo Activities of Amoxicillin and Amoxicillin-Clavulanate against Streptococcus pneumoniae: Application to Breakpoint Determinations
- Pharmacodynamic Assessment of Gatifloxacin against Streptococcus pneumoniae
- Cefotaxime breakpoint for Streptococcus pneumoniae.
- Pharmacodynamic Assessment of Ertapenem (MK-0826) against Streptococcus pneumoniae in a Murine Neutropenic Thigh Infection Model
- Bactericidal activities of cefprozil, penicillin, cefaclor, cefixime, and loracarbef against penicillin-susceptible and -resistant Streptococcus pneumoniae in an in vitro pharmacodynamic infection model.
